Ankaflavin ameliorates steatotic liver ischemia-reperfusion injury in mice.

Abstract

BACKGROUND:

It is well-known that steatotic liver is more susceptible to ischemia-reperfusion (I/R) injury during liver transplantation, liver resection and other liver surgeries. The increasing incidence of non-alcoholic fatty liver disease (NAFLD) decreases the availability of liver donors. Although steatotic liver is now accepted as a source of liver for transplantation, NAFLD exacerbates the liver injury after liver surgery. The present study was to investigate the protective role of ankaflavin in steatotic liver I/R injury.

METHODS:

The model of fatty liver mice was induced with high fat diet in four weeks, ankaflavin or vehicle (saline) was administrated by gavage once a day for one week. The animals were subjected to partial hepatic I/R. Blood samples were collected to measure serum aminotransferases. The liver tissues were used to examine liver steatosis, apoptosis of hepatocytes, hepatic oxidative stress, Kupffer cells and inflammatory cytokines. The effects of ankaflavin on inflammatory cytokines were evaluated in isolated Kupffer cells from the steatotic liver.

RESULTS:

Ankaflavin reduced liver steatosis in high fat diet mice. Compared with normal mice, I/R induced more damage to the mice with steatosis, such as hepatocyte apoptosis, inflammatory cytokines (TNF-alpha, IL-6 and IL-1 beta), serum aminotransferases and thiobarbituric acid reactive substances. Importantly, ankaflavin administration significantly attenuated these changes. In addition, ankaflavin significantly decreased the proliferation of Kupffer cells and the expression of TNF-alpha, IL-6 and IL-1 beta protein in isolated Kupffer cells stimulated by TNF-alpha.

CONCLUSION:

Ankaflavin has protective effects against I/R injury through anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms in fatty livers, these effects are at least partially mediated by inhibiting Kupffer cell functions.

• Authors: Hao-Jun Yang, Li-Ming Tang, Xian-Ju Zhou, Jun Qian, Jie Zhu, Ling Lu, Xue-Hao Wang
• Journal: Hepatobiliary & pancreatic diseases international : HBPD INT (Hepatobiliary Pancreat Dis Int) Vol. 14 Issue 6 Pg. 619-25 (Dec 2015) ISSN: 1499-3872 [Print] Singapore
• PMID: 26663010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Biomarkers
• Cytokines
• Flavins
• ankaflavin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Biomarkers (blood)
• Cell Proliferation (drug effects)
• Cytokines (metabolism)
• Cytoprotection
• Disease Models, Animal
• Flavins (pharmacology)
• Hepatocytes (drug effects, metabolism, pathology)
• Kupffer Cells (drug effects, metabolism, pathology)
• Liver (drug effects, metabolism, pathology, surgery)
• Male
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (blood, complications, drug therapy, pathology)
• Oxidative Stress (drug effects)
• Reperfusion Injury (blood, etiology, pathology, prevention & control)